Abstract

Introduction

Haemophilic arthropathy following recurrent joint bleedings is one of the major disease-related
complications in people with haemophilia (PWH), leading to mostly chronic joint pain.
Since many antinociceptive principles interfere with the clotting system, PWH are
restricted in treatment options, thereby defining a medical need for novel therapeutic
principles. However, we lack the availability of an animal model for joint pain in
haemophilic arthropathy for testing these.

Methods

In this study, we aimed to validate the rat model of repeated autologous intraarticular
blood injections specifically for pain-related behavior. During an observation period
of 50 days, groups of animals were injected weekly into one knee joint with either
whole blood or cellular/plasma components.

Results

Injections induced primary hyperalgesia starting after the third injection, accompanied
by mild functional gait changes and joint swelling. Secondary hyperalgesia and quantitative
gait disturbances were not observed. This phenotype was most prominent in whole blood
injected animals, with effect sizes of cells and plasma being additive. In order to
differentiate haemophilia-related arthropathy from traumatic joint bleeding, another
group was injected with whole blood only once, which did not cause any alterations.

Conclusions

Repeated autologous intraarticular injections of blood showed a time course, inflammatory
response and reduction in pain thresholds similar to the signs and symptoms observed
in PWH. Therefore, this model may be utilised in the future for testing novel antinociceptive
principles in haemophilia-associated joint pain.